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Background <p>Continuous positive airway pressure (CPAP) remains the cornerstone of therapy for obstructive sleep apnea, yet its impact on preventing cardiovascular disease remains uncertain. Despite widespread clinical use, randomized controlled trials have not shown cardiovascular benefits with CPAP. Emerging evidence suggests that obstructive sleep apnea is a heterogeneous disease, and a uniform approach to treatment may obscure potential benefits or harm for individuals.</p> Methods <p>To address this, we applied causal survival forest analysis to data from the SAVE trial (n = 2,687), the largest clinical trial evaluating CPAP for cardiovascular disease prevention, to estimate individualized treatment effect scores for each participant.</p> Results <p>Our model reveals significant heterogeneity in treatment response across the cohort (area under the target operator characteristic curve 2.6; 95% confidence interval 2.03-4.55; p &lt; 0.001). Survival analysis demonstrates that participants in the tertile predicted to benefit from CPAP experienced a 100-fold improvement in event-free survival when randomized to CPAP (p &lt; 0.001), whereas those in the tertile predicted to be harmed experienced a &gt; 100-fold increase in major adverse cardiovascular outcomes (p &lt; 0.001).</p> Conclusions <p>To our knowledge, these findings provide the first evidence of individualized treatment effect estimates for CPAP therapy in obstructive sleep apnea. These results also highlight the potential for precision medicine approaches to guide treatment decisions, reduce cardiovascular disease risk, and avoid harm in susceptible individuals.</p>

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Individualized treatment effects of CPAP on secondary cardiovascular outcomes in non-sleepy obstructive sleep apnea patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月13日

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  • Oren Cohen,
  • Zainab Al-Taie,
  • Vaishnavi Kundel,
  • Samira Khan,
  • Kavya Devarakonda,
  • Vi Le,
  • Philip M. Robson,
  • Craig S. Anderson,
  • Mathias Baumert,
  • Kelly Loffler,
  • R. Doug McEvoy,
  • Mayte Suárez-Fariñas,
  • Neomi A. Shah

摘要

Background

Continuous positive airway pressure (CPAP) remains the cornerstone of therapy for obstructive sleep apnea, yet its impact on preventing cardiovascular disease remains uncertain. Despite widespread clinical use, randomized controlled trials have not shown cardiovascular benefits with CPAP. Emerging evidence suggests that obstructive sleep apnea is a heterogeneous disease, and a uniform approach to treatment may obscure potential benefits or harm for individuals.

Methods

To address this, we applied causal survival forest analysis to data from the SAVE trial (n = 2,687), the largest clinical trial evaluating CPAP for cardiovascular disease prevention, to estimate individualized treatment effect scores for each participant.

Results

Our model reveals significant heterogeneity in treatment response across the cohort (area under the target operator characteristic curve 2.6; 95% confidence interval 2.03-4.55; p < 0.001). Survival analysis demonstrates that participants in the tertile predicted to benefit from CPAP experienced a 100-fold improvement in event-free survival when randomized to CPAP (p < 0.001), whereas those in the tertile predicted to be harmed experienced a > 100-fold increase in major adverse cardiovascular outcomes (p < 0.001).

Conclusions

To our knowledge, these findings provide the first evidence of individualized treatment effect estimates for CPAP therapy in obstructive sleep apnea. These results also highlight the potential for precision medicine approaches to guide treatment decisions, reduce cardiovascular disease risk, and avoid harm in susceptible individuals.